The etiologic agent of acquired immunodeficiency syndrome (AIDS) is the human immunodeficiency virus (HIV). HIV is a genomically and biologically heterogeneous virus; many reports have noted that a wide variety of HIV strains exist with differing nucleotide sequences and widely differing biological properties. Differential replication of HIV isolates in vitro has been reported in established lines of T cells, B cells, monocytes and in PHA stimulated PBL. Recent studies demonstrate that many HIV variants exists within an infected individual at any one time and that the clinical condition of the patient correlates with the collective biological properties of those viruses in vitro. Although it is speculated that the differences in replication kinetics of HIV isolates are determined by differences in the viral nonstructural proteins and the control elements of the LTR, the viral determinants responsible for differential replication, tropism and cytopathic effects are not known. If the biological diversity in vitro has relevance to replication in vivo, an understanding of the genetic factors that govern the biological properties of the virus would contribute to efforts in controlling pathogenicity. To determine the regions of the viral genome responsible for the differential replication, tropism and cytopathic effects of HIVs, a series of hybrid viruses will be constructed from molecular clones of several well characterized HIV isolates. The replication potential, tropism and cytopathogenicity of the hybrid and parental viruses will be determined in a variety of cells. The long term objective is to understand the molecular basis of the distinctive biological properties of HIVS.